Physiological measurement using wearable device

ABSTRACT

A wearable device includes a detector configured to detect a response signal transmitted from a portion of subsurface vasculature, the response signal being related to binding of a clinically-relevant analyte to functionalized particles present in a lumen of the subsurface vasculature. Program instructions stored in a computer readable medium of the device, and executable by a processor, may cause the device to determine a concentration of the clinically-relevant analyte based on the response signal detected by the detector; determine whether a medical condition is indicated based on at least the concentration of the clinically-relevant analyte; and, in response to a determination that the medical condition is indicated, transmit data representative of the medical condition via the communication interface. The device may also include a signal source configured to transmit an interrogating signal into the portion of subsurface vasculature, thereby generating a response signal in response to the interrogating signal.

BACKGROUND

Unless otherwise indicated herein, the materials described in thissection are not prior art to the claims in this application and are notadmitted to be prior art by inclusion in this section.

A number of scientific methods have been developed in the medical fieldto measure physiological conditions of a person. For example, devicesexist that may be used to measure physiological conditions such as auser's heart rate, blood pressure, skin temperature, breathing rate,etc.

Additional physiological parameters may be obtained by detecting and/ormeasuring one or more analytes in a person's blood. The one or moreanalytes could be any analytes that, when present in or absent from theblood, or present at a particular concentration or range ofconcentrations, may be indicative of a medical condition or health ofthe person. The one or more analytes could include enzymes, hormones,proteins, cells or other molecules.

In a typical scenario, a person's blood is drawn and sent to a lab wherea variety of tests are performed to measure various analyte levels andparameters in the blood. The variety of tests may be referred to as“blood work,” where the blood is tested for the presence of variousdiseases, or analyte levels such as cholesterol levels, etc. For mostpeople, the blood tests are infrequent, and an abnormal analyte levelindicative of a medical condition may not be identified until the nextblood test is performed.

Even in the case of relatively frequent blood testing, such as may befound with those with diabetes, who regularly draw blood to test forblood glucose concentrations, those blood tests are typically performedwhen the user is awake, although the blood glucose levels (and potentialvariations in such levels) occurring during the night could provideimportant information to assist a physician in assessing that person'smedical condition.

SUMMARY

Some embodiments of the present disclosure provide a wearable device,including: (i) a mount configured to mount the wearable device to anexternal body surface proximate to a portion of subsurface vasculature;(ii) a detector configured to detect a response signal transmitted fromthe portion of subsurface vasculature, wherein the response signal isrelated to binding of a clinically-relevant analyte to functionalizedparticles present in a lumen of the subsurface vasculature, thefunctionalized particles configured to bind to the clinically-relevantanalyte; (iii) a communication interface; (iv) a processor; (v) acomputer-readable medium; and (vi) program instructions stored in thecomputer-readable medium, wherein the program instructions areexecutable by the processor to cause the wearable device to performfunctions comprising: detecting the presence or absence of theclinically-relevant analyte based on the response signal detected by thedetector; and determining whether a medical condition is indicated basedon at least the presence or absence of the clinically-relevant analyte;and in response to a determination that the medical condition isindicated, transmitting data representative of the medical condition viathe communication interface. In some examples the body surface comprisesa wrist. The mount may comprise a wristband or cuff. The functions mayfurther comprise determining a concentration of the clinically-relevantanalyte based on the response signal detected by the detector; anddetermining whether a medical condition is indicated based on at leastthe concentration of the clinically-relevant analyte.

In a further example, the wearable device comprises a signal sourceconfigured to transmit an interrogating signal into the portion ofsubsurface vasculature, wherein the response signal is generated inresponse to the interrogating signal. The interrogating signal maycomprise an electromagnetic pulse. The electromagnetic pulse may be aradio frequency (RF) pulse and the response signal may comprise amagnetic resonance signal. In a further example, the interrogatingsignal comprises a time-varying magnetic field. The response signal maycomprise an externally-detectable physical motion of the functionalizedparticles due to the time-varying magnetic field. In a further example,the interrogating signal comprises electromagnetic radiation having awavelength between about 400 nanometers and about 1600 nanometers. Theinterrogating signal may comprise electromagnetic radiation having awavelength between about 500 nanometers and about 1000 nanometers. Insome examples, the functionalized particles comprise a fluorophore, theresponse signal may comprise fluorescence radiation transmitted by thefluorophore in response to the interrogating signal. In still furtherexamples, the functionalized particles comprise a chemo-luminescentmarker, and wherein the response signal comprises fluorescence radiationtransmitted by the chemo-luminescent marker in response to a chemicalreaction initiated, at least in part, by the binding of the targetanalyte to the particle upon undergoing a chemical reaction.

In some examples, the functionalized particles are magnetic and thewearable device further comprises a magnet configured to direct amagnetic field into the portion of subsurface vasculature, wherein themagnetic field is sufficient to cause functionalized magnetic particlesto collect in a lumen of the portion of subsurface vasculature.

The wearable device may, in some examples, comprise a user interface,and the functions may further comprise: reporting the presence orabsence of the clinically relevant analyte via the user interface. Thefunctions may further comprise: in response to a determination that themedical condition is indicated, generating an alert via the userinterface.

In still further examples, the functions further comprise: controllingthe signal source to transmit interrogating signals at presetmeasurement times; receiving, from the detector, data representative ofresponse signals transmitted from the portion of subsurface vasculaturein response to the interrogating signals transmitted at the presetmeasurement times; detecting, for each preset measurement time, thepresence or absence of the clinically-relevant analyte based on theresponse signal detected by the detector at that measurement time; anddetermining, for each preset measurement time, whether the medicalcondition is indicated based on at least the presence or absence of theclinically-relevant analyte. The functions may further comprise:determining, for each preset measurement time, a correspondingconcentration of the clinically-relevant analyte based on the responsesignal detected by the detector at that measurement time; anddetermining, for each preset measurement time, whether the medicalcondition is indicated based on at least the corresponding concentrationof the clinically relevant analyte.

Some embodiments of the present disclosure provide a method, including:(i) transmitting, from a wearable device, an interrogating signal intothe portion of the subsurface vasculature; (ii) detecting, by thewearable device, a response signal transmitted from the portion ofsubsurface vasculature in response to the interrogating signal, whereinthe response signal is related to binding of a clinically-relevantanalyte to functionalized particles present in a lumen of the subsurfacevasculature, the functionalized particles being configured to bind tothe clinically-relevant analyte; (iii) detecting, by the wearabledevice, the presence or absence of the clinically-relevant analyte basedon the response signal; and (iv) determining, by the wearable device,whether a medical condition is indicated based on at least the presenceor absence of the clinically-relevant analyte; wherein the wearabledevice is configured to be mounted to a body surface of a human subjectproximate to a portion of subsurface vasculature. The method may furthercomprise: determining, by the wearable device, a concentration of theclinically-relevant analyte based on the response signal; anddetermining, by the wearable device, whether a medical condition isindicated based on at least the concentration of the clinically-relevantanalyte.

Some embodiments of the present disclosure provide a wearable device,including: (i) a mount configured to externally mount the wearabledevice to the surface of a wrist proximate to a portion of subsurfacevasculature; (ii) a magnet configured to direct a magnetic field intothe portion of subsurface vasculature, wherein the magnetic field issufficient to cause functionalized magnetic particles to collect in alumen of the portion of the subsurface vasculature, and wherein thefunctionalized magnetic particles are configured to bind to aclinically-relevant analyte; (iii) a signal source configured totransmit an electromagnetic pulse interrogating signal into the portionof subsurface vasculature; (iv) a detector configured to detect amagnetic resonance response signal transmitted from the portion ofsubsurface vasculature in response to the interrogating signal, whereinthe response signal is related to binding of the clinically-relevantanalyte to the functionalized magnetic particles; and (v) a userinterface; wherein the mount is configured to mount the signal sourceand detector to an anterior surface of a wrist and the user interface toa posterior surface of a wrist. The electromagnetic pulse may be a radiofrequency (RF) pulse. In some examples, the mount comprises a wristband.

In some examples, the wearable device further comprises: a processor; acomputer-readable medium; and program instructions stored in thecomputer-readable medium, wherein the program instructions areexecutable by the processor to cause the wearable device to performfunctions comprising: detecting the presence or absence of theclinically-relevant analyte based on the response signal detected by thedetector; and determining whether a medical condition is indicated basedon at least the presence or absence of the clinically-relevant analyte.The wearable device may further comprise: a communication interface,wherein the functions further comprise: in response to a determinationthat the medical condition is indicated, transmitting datarepresentative of the medical condition via the communication interface.The communication interface may be a wireless communication interface.

These as well as other aspects, advantages, and alternatives, willbecome apparent to those of ordinary skill in the art by reading thefollowing detailed description, with reference where appropriate to theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of an example wearable device.

FIG. 2A is a perspective top view of an example wrist-mounted device,when mounted on a wearer's wrist.

FIG. 2B is a perspective bottom view of an example wrist-mounted deviceshown in FIG. 2A, when mounted on a wearer's wrist.

FIG. 3A is a perspective bottom view of an example wrist-mounted device,when mounted on a wearer's wrist.

FIG. 3B is a perspective top view of an example wrist-mounted deviceshown in FIG. 3A, when mounted on a wearer's wrist.

FIG. 3C is a perspective view of an example wrist-mounted device shownin FIGS. 3A and 3B.

FIG. 4A is a perspective view of an example wrist-mounted device.

FIG. 4B is a perspective bottom view of an example wrist-mounted deviceshown in FIG. 4A.

FIG. 5 is a perspective view of an example wrist-mounted device.

FIG. 6 is a perspective view of an example wrist-mounted device.

FIG. 7 is a block diagram of an example system that includes a pluralityof wrist mounted devices in communication with a server.

FIG. 8 is a functional block diagram of an example wearable device.

FIG. 9 is a functional block diagram of an example wearable device.

FIG. 10 is a flowchart of an example method for operating a wearabledevice.

FIG. 11A is side partial cross-sectional view of a wrist-mounted device,while on a human wrist.

FIG. 11B is side partial cross-sectional view of a wrist-mounted device,while on a human wrist.

FIG. 12A is side partial cross-sectional view of a wrist-mounted device,while on a human wrist.

FIG. 12B is side partial cross-sectional view of a wrist-mounted device,while on a human wrist.

FIG. 13A is side partial cross-sectional view of a wrist-mounted device,while on a human wrist.

FIG. 13B is side partial cross-sectional view of a wrist-mounted device,while on a human wrist.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying figures, which form a part hereof. In the figures, similarsymbols typically identify similar components, unless context dictatesotherwise. The illustrative embodiments described in the detaileddescription, figures, and claims are not meant to be limiting. Otherembodiments may be utilized, and other changes may be made, withoutdeparting from the scope of the subject matter presented herein. It willbe readily understood that the aspects of the present disclosure, asgenerally described herein, and illustrated in the figures, can bearranged, substituted, combined, separated, and designed in a widevariety of different configurations, all of which are explicitlycontemplated herein.

I. Overview

A wearable device can automatically detect and measure a plurality ofphysiological parameters of a person wearing the device. Thephysiological parameters could include any parameters that may relate tothe health of the person wearing the wearable device. For example, thewearable device could include sensors for measuring blood pressure,pulse rate, skin temperature, etc. At least some of the physiologicalparameters may be obtained by the wearable device non-invasivelydetecting and/or measuring one or more analytes in blood circulating insubsurface vasculature proximate to the wearable device. The one or moreanalytes could be any analytes that, when present in or absent from theblood, or present at a particular concentration or range ofconcentrations, may be indicative of a medical condition or health ofthe person wearing the device. For example, the one or more analytescould include enzymes, hormones, proteins, cells or other molecules.

The wearable device can include a mount that is configured to mount thedevice to a specific surface of the person's body, more particularly, toa body location where subsurface vasculature is readily observable. Forexample, the wearable device can include a wristband for mounting thewearable device on the wrist. In this position, the wearable device maybe only about 2-4 millimeters away from the midpoint of an artery,capillary or vein in the wrist.

In an example embodiment, the wearable device obtains at least some ofthe health-related information by detecting the binding of aclinically-relevant analyte to functionalized particles, for example,microparticles or nanoparticles introduced into a lumen of thesubsurface vasculature. The term “binding” is understood in its broadestsense to also include a detectable interaction between the clinicallyrelevant analyte and the functionalized particles. The particles canhave a diameter that is less than about 20 micrometers. In someembodiments, the particles have a diameter on the order of about 10 nmto 1 μm. In further embodiments, small particles on the order of 10-100nm in diameter may be assembled to form a larger “clusters” or“assemblies on the order of 1-10 micrometers. Those of skill in the artwill understand a “particle” in its broadest sense and that it may takethe form of any fabricated material, a molecule, cryptophan, a virus, aphage, etc. Further, a particle may be of any shape, for example,spheres, rods, non-symmetrical shapes, etc.

In some examples, the particles may be magnetic and can be formed from aparamagnetic, super-paramagnetic or ferromagnetic material or any othermaterial that responds to a magnetic field. Alternatively, the particlesmay also be made of non-magnetic materials such as polystyrene.

The particles, or a group of several particles in a complex, may befunctionalized with a receptor that has a specific affinity to bind toor interact with a clinically relevant analyte. The receptor may beinherent to the particle itself. For example, the particle itself may bea virus or a phage with an inherent affinity for certain analytes.Additionally or alternatively, the particles can be functionalized bycovalently attaching a receptor that specifically binds or otherwiserecognizes a particular clinically-relevant analyte. The functionalizedreceptor can be an antibody, peptide, nucleic acid, phage, bacteria,virus, or any other molecule with a defined affinity for a targetanalyte. Other compounds or molecules, such as fluorophores orautofluorescent or luminescent markers, which may assist ininterrogating the particles in vivo, may also be attached to theparticles.

The functionalized particles can be introduced into the person's bloodstream by injection, ingestion, inhalation, transdermally, or in someother manner. Where magnetic particles are used, the wearable device mayinclude a magnet that can direct into the portion of subsurfacevasculature a magnetic field that is sufficient to cause thefunctionalized magnetic particles to collect in a lumen of that portionof subsurface vasculature. However, measurements may be taken withoutlocalized “collection” of the functionalized particles. The wearabledevice may be configured to activate the magnetic periodically, such asat certain times of every day (e.g., every hour).

The wearable device may further include one or more data collectionsystems for interrogating, in a non-invasive manner, the functionalizedparticles present in a lumen of the subsurface vasculature in the localarea of the wearable device. In one example, the wearable deviceincludes a signal source for transmitting an interrogating signal thatcan penetrate the wearer's skin into the portion of subsurfacevasculature and a detector for detecting a response signal that istransmitted from the portion of subsurface vasculature in response tothe interrogating signal. The interrogating signal can be any kind ofsignal that is benign to the wearer and results in a response signalthat can be used to detect binding of the clinically-relevant analyte tothe functionalized particles. In one example, the interrogating signalis a radio frequency (RF) signal and the response signal is a magneticresonance signal, such as nuclear magnetic resonance (NMR). In anotherexample, where the functionalized particles include a fluorophore, theinterrogating signal is an optical signal with a wavelength that canexcite the fluorophore and penetrate the skin or other tissue andsubsurface vasculature (e.g., a wavelength in the range of about 500 toabout 1000 nanometers), and the response signal is fluorescenceradiation from the fluorophore that can penetrate the subsurfacevasculature and tissue to reach the detector.

Further, in some cases, an interrogating signal may not be necessary toproduce a response signal. For example, where the functionalizedparticles include an autofluorescent or luminescent marker, aninterrogating signal may not be necessary. In some examples, thefunctionalized particles may include a chemo-luminescent markerconfigured to produce a response signal in the form of fluorescenceradiation produced in response to a chemical reaction initiated, atleast in part, to the binding of the target analyte to the particle.

The wearable device can also include one or more data collection systemsthat do not make use of functionalized particles. For example, thewearable device can include sensors for measuring blood pressure, pulserate, skin temperature, or other parameters. If in the form of awristband, the wearable device may also include a watch face fordisplaying the time and/or date.

In addition, the wearable device may be configured to analyze the datathat it collects. For example, the wearable device may include acomputing device that is configured to detect the presence or absence ofthe clinically-relevant analyte and, in some examples, to furtherdetermine a concentration of the clinically-relevant analyte based onthe response signal detected by the detector and determine whether amedical condition is indicated based on at least the presence, absenceand/or concentration of the clinically-relevant analyte. In someexamples, a medical condition may be indicated based, at least in part,on the fact that a particular clinically-relevant analyte is absent fromthe blood or is present in the blood at a lower than normalconcentration, such as when a target analyte is being taken up by atumor. The wearable device may be configured to conduct such an“inverse” test by recognizing that a particular class of functionalizedparticles does not produce a responsive signal proportional to theamount of that class of particles introduced into a lumen of thevasculature. The wearable device may also include a user interface thatcan display the results of the data analysis, such as whether theclinically-relevant analyte is present and in what concentration. Inthis way, the person wearing the device can be made aware of medicalconditions in real time. The wearable device may also be configured toproduce an auditory or tactile (vibration) response to alert the personwearing the device of a medical condition.

The wearable device may further include a communication interface fortransmitting the results of the data analysis to medical personneland/or receiving instructions or recommendations based on a medicalpersonnel or remote computing device's interpretation of those results.In some examples, the communication interface is a wirelesscommunication interface. The communication interface may also include auniversal serial bus (USB) interface, a secure digital (SD) cardinterface, a wired interface, or any other appropriate interface forcommunicating data from the device to a server. The term “server” mayinclude any system or device that responds to requests across a computernetwork to provide, or helps to provide, a network service, and mayinclude servers run on dedicated computers, mobile devices, and thoseoperated in a cloud computing network.

As one possible example, the presence of an unstable arterial plaquethat could potentially cause a heart attack or stroke is oftenassociated with an increase in certain protein markers in the blood. Aperson who may be at risk for this medical condition may take particlesthat are functionalized to bind to such protein markers and may wear onhis or her wrist a device that is configured to periodically (e.g.,every hour) collect and interrogate the functionalized particles todetermine the concentrations of the protein markers. If the devicedetermines that the concentrations of the protein markers indicate anelevated risk of a heart attack or other life-threatening episode, thedevice may generate an alert through the user interface (e.g., anaudible alarm) so that the person wearing the device can seek immediatemedical attention.

The wearable device may obtain data in each of a plurality ofmeasurement periods. The length of the measurement period may be set onthe device itself or may be set remotely, for example, by instructionfrom a remote server. The device may be configured with many measurementperiods each day—for example, continuous, every second, every minute,every hour, every 6 hours, etc.—or may be configured to takemeasurements once a week or once a month. The measurement periods canextend through a plurality of consecutive days (such as 30 or moredays), and each of the consecutive days can include multiple measurementperiods. In one example, the wearable device could measure thephysiological parameters every hour, so that each of the consecutivedays includes twenty-four measurement periods. In other examples, thewearable device could measure the physiological parameters morefrequently or less frequently, or the wearable device could measure someof the physiological parameters more frequently than others.

Data representative of the physiological parameters may be used todevelop an individual baseline profile for the wearer of the wearabledevice. The baseline profile may include patterns for how one or more ofthe wearer's physiological parameters typically change over time, suchas during the course of a day, a week, or a month. The baseline profilemay be developed on the wearable device itself (such as by a processor),or it may be developed by a remote server.

The wearable device may be configured to transmit certain data, such asthe data representative of the physiological parameters, the baselineprofile, etc., to a server, for example, via a wireless communicationinterface in the wearable device. In this way, the server may receivefrom the wearable device data regarding the plurality of physiologicalparameters for each of the plurality of measurement periods. Thewearable device may be configured to automatically transmit the data toa server, may be configured to transmit on command of the wearer, or maybe configured to transmit on instruction from a remote server. Further,the device may be configured to automatically transmit the data at theend of each measurement period, or at some more frequent or infrequentrate. For example, the device could be configured to transmit every fiveminutes, at the end of each day, at the end of the month, at nighttimeonly, etc.

After a baseline profile for a wearer of the device has been developed,either by the device or the server, additional data regarding thephysiological parameters may be collected over additional measurementperiods by the wearable device and may be compared to the baselineprofile. Such comparison may be carried out on the wearable deviceitself, or by a remote server upon transmission of the additional datato the server. If the additional data is consistent with the patternsembodied in the baseline profile, the server may determine that thewearer's condition has not changed. On the other hand, if the additionaldata deviates from the patterns embodied in the baseline profile, theserver may determine that the wearer's condition has changed. The changein condition could, for example, indicate that the wearer has developeda disease, disorder, or other adverse medical condition or may be atrisk for a severe medical condition, such as a stroke or a heart attack,in the near future.

When a change in condition is detected, a clinical protocol may beconsulted to generate one or more recommendations that are appropriatefor the wearer's change in condition. For example, a recommendation thatthe wearer take a particular medication or supplement, schedule anappointment with a medical professional, go to the hospital to seekimmediate medical attention, abstain from certain activities, etc. maybe generated. The clinical protocol may be developed based, at least inpart, on correlations between analyte concentration and health state ofthe wearer of the device, any known health information or medicalhistory of the wearer, and/or on recognized standards of care in themedical field. Such actions may be carried out by a processor on thewearable device, or by a remote server.

Further, the wearable device may be configured to accept inputs from thewearer regarding his or her health state. The inputs may be subjectiveindicia regarding how the person is feeling or any symptoms he or she isexperiencing at that time, such as, “feeling cold,” “feeling tired,”“stressed,” “feeling rested and energetic,” “pollen allergy symptomstoday,” etc. Such inputs from the user may be used to complement thephysiological parameter data and establish correlations between theblood analysis results and health state.

The wearable device may be configured to accept, or the server may beconfigured to receive from some other source, certain environmentalinformation. For example, information regarding the general health stateof the population, such as when influenza or other viral outbreak hasoccurred, may be input into the system. Further, other generalinformation that may affect the health of the population, such as dailypollen counts, pollution levels or the weather conditions may be inputinto the system. Such information may further be used to complement thephysiological parameter data collected from individual wearers andpopulations of wearers of the device and establish correlations betweenthe blood analysis results, health state and environmental factors.

Once generated, either by the server or the wearable device itself, thewearable device may provide an indication of the one or morerecommendations via a user interface on the wearable device. Theindication could be any indication that can be noticed by the personwearing the wearable device. For example, the indication could include avisual component (e.g., textual or graphical information on a display),an auditory component (e.g., an alarm sound), and/or tactile component(e.g., a vibration).

The wearable device and/or the server may also be configured to receiveinformation regarding the actual health state of the wearer of thewearable device. This information may be received at the end of eachanalyte measurement period, or at some other frequency. In one example,the wearable device itself, or some external computing device, may beconfigured to accept such information as inputs and transmit it to theserver or medical professional(s). Further, the wearable device and/orthe server may be configured to derive correlations between the reportedhealth state of the wearer, and the blood analyte measurement(s)transmitted by the wearable device. For example, the wearable deviceand/or the server may analyze the blood analyte data and the healthstate data and detect that the wearer has experienced certain adversehealth conditions, such as a migraine or a heart attack, when an analytereached a certain concentration. The wearable device and/or the servermay use this correlation data to generate recommendations for thewearer, or to develop a clinical protocol.

The server that receives the data from the wearable device may receivesimilar data from a plurality of other, similar wearable devices. Inthis way, the server can collect data regarding a plurality of humansubjects. This data, including both the analyte measurements and theindications of health state, may, in turn, be used to develop one ormore clinical protocols used by the server to generate recommendationsand/or used by medical professionals to provide medical care and adviceto their patients. This data may further be used to recognizecorrelations between blood analytes and health conditions among thepopulation. Health professionals may further use this data to diagnoseand prevent illness and disease, prevent serious clinical events in thepopulation, and to update clinical protocols, courses of treatment, andthe standard of care.

It should be understood that the above embodiments, and otherembodiments described herein, are provided for explanatory purposes, andare not intended to be limiting.

Further, the term “medical condition” as used herein should beunderstood broadly to include any disease, illness, disorder, injury,condition or impairment—e.g., physiologic, psychological, cardiac,vascular, orthopedic, visual, speech, or hearing—or any situationrequiring medical attention.

II. Example Wearable Devices

A wearable device 100 can automatically measure a plurality ofphysiological parameters of a person wearing the device. The term“wearable device,” as used in this disclosure, refers to any device thatis capable of being worn at, on or in proximity to a body surface, suchas a wrist, ankle, waist, chest, or other body part. In order to take invivo measurements in a non-invasive manner from outside of the body, thewearable device may be positioned on a portion of the body wheresubsurface vasculature is easily observable, the qualification of whichwill depend on the type of detection system used. The device may beplaced in close proximity to the skin or tissue, but need not betouching or in intimate contact therewith. A mount 110, such as a belt,wristband, ankle band, etc. can be provided to mount the device at, onor in proximity to the body surface. The mount 110 may prevent thewearable device from moving relative to the body to reduce measurementerror and noise. In one example, shown in FIG. 1, the mount 110, maytake the form of a strap or band 120 that can be worn around a part ofthe body. Further, the mount 110 may be an adhesive substrate foradhering the wearable device 100 to the body of a wearer.

A measurement platform 130 is disposed on the mount 110 such that it canbe positioned on the body where subsurface vasculature is easilyobservable. An inner face 140 of the measurement platform is intended tobe mounted facing to the body surface. The measurement platform 130 mayhouse the data collection system 150, which may include at least onedetector 160 for detecting at least one physiological parameter, whichcould include any parameters that may relate to the health of the personwearing the wearable device. For example, the detector 160 could beconfigured to measure blood pressure, pulse rate, respiration rate, skintemperature, etc. At least one of the detectors 160 is configured tonon-invasively measure one or more analytes in blood circulating insubsurface vasculature proximate to the wearable device. In anon-exhaustive list, detector 160 may include any one of an optical(e.g., CMOS, CCD, photodiode), acoustic (e.g., piezoelectric,piezoceramic), electrochemical (voltage, impedance), thermal, mechanical(e.g., pressure, strain), magnetic, or electromagnetic (e.g., magneticresonance) sensor. The components of the data collection system 150 maybe miniaturized so that the wearable device may be worn on the bodywithout significantly interfering with the wearer's usual activities.

In some examples, the data collection system 150 further includes asignal source 170 for transmitting an interrogating signal that canpenetrate the wearer's skin into the portion of subsurface vasculature,for example, into a lumen of the subsurface vasculature. Theinterrogating signal can be any kind of signal that is benign to thewearer, such as electromagnetic, magnetic, optic, acoustic, thermal,mechanical, and results in a response signal that can be used to measurea physiological parameter or, more particularly, that can detect thebinding of the clinically-relevant analyte to the functionalizedparticles. In one example, the interrogating signal is anelectromagnetic pulse (e.g., a radio frequency (RF) pulse) and theresponse signal is a magnetic resonance signal, such as nuclear magneticresonance (NMR). In another example, the interrogating signal is atime-varying magnetic field, and the response signal is anexternally-detectable physical motion due to the time-varying magneticfield. The time-varying magnetic field modulates the particles byphysical motion in a manner different from the background, making themeasier to detect. In a further example, the interrogating signal is anelectromagnetic radiation signal. In particular, the interrogatingsignal may be electromagnetic radiation having a wavelength betweenabout 400 nanometers and about 1600 nanometers. The interrogating signalmay, more particularly, comprise electromagnetic radiation having awavelength between about 500 nanometers and about 1000 nanometers. Insome examples, the functionalized particles include a fluorophore. Theinterrogating signal may therefore be an electromagnetic radiationsignal with a wavelength that can excite the fluorophore and penetratethe skin or other tissue and subsurface vasculature (e.g., a wavelengthin the range of about 500 to about 1000 nanometers), and the responsesignal is fluorescence radiation from the fluorophore that can penetratethe subsurface vasculature and tissue to reach the detector.

In some cases, an interrogating signal is not necessary to measure oneor more of the physiological parameters and, therefore, the wearabledevice 100 may not include a signal source 170. For example, thefunctionalized particles include an autofluorescent or luminescentmarker, such as a fluorophore, that will automatically emit a responsesignal indicative of the binding of the clinically-relevant analyte tothe functionalized particles, without the need for an interrogatingsignal or other external stimulus. In some examples, the functionalizedparticles may include a chemo-luminescent marker configured to produce aresponse signal in the form of fluorescence radiation produced inresponse to a chemical reaction initiated, at least in part, to thebinding of the target analyte to the particle.

A collection magnet 180 may also be included in the data collectionsystem 150. In such embodiments, the functionalized particles may alsobe made of or be functionalized with magnetic materials, such asferromagnetic, paramagnetic, super-paramagnetic, or any other materialthat responds to a magnetic field. The collection magnet 180 isconfigured to direct a magnetic field into the portion of subsurfacevasculature that is sufficient to cause functionalized magneticparticles to collect in a lumen of that portion of subsurfacevasculature. The magnet may be an electromagnet that may be turned onduring measurement periods and turned off when a measurement period iscomplete so as to allow the magnetic particles to disperse through thevasculature.

The wearable device 100 may also include a user interface 190 via whichthe wearer of the device may receive one or more recommendations oralerts generated either from a remote server or other remote computingdevice, or from a processor within the device. The alerts could be anyindication that can be noticed by the person wearing the wearabledevice. For example, the alert could include a visual component (e.g.,textual or graphical information on a display), an auditory component(e.g., an alarm sound), and/or tactile component (e.g., a vibration).Further, the user interface 190 may include a display 192 where a visualindication of the alert or recommendation may be displayed. The display192 may further be configured to provide an indication of the measuredphysiological parameters, for instance, the concentrations of certainblood analytes being measured.

In one example, the wearable device is provided as a wrist-mounteddevice, as shown in FIGS. 2A, 2B, 3A-3C, 4A, 5B, 6 and 7. Thewrist-mounted device may be mounted to the wrist of a living subjectwith a wristband or cuff, similar to a watch or bracelet. As shown inFIGS. 2A and 2B, the wrist mounted device 200 may include a mount 210 inthe form of a wristband 220, a measurement platform 230 positioned onthe anterior side 240 of the wearer's wrist, and a user interface 250positioned on the posterior side 260 of the wearer's wrist. The wearerof the device may receive, via the user interface 250, one or morerecommendations or alerts generated either from a remote server or otherremote computing device, or alerts from the measurement platform. Such aconfiguration may be perceived as natural for the wearer of the devicein that it is common for the posterior side 260 of the wrist to beobserved, such as the act of checking a wrist-watch. Accordingly, thewearer may easily view a display 270 on the user interface. Further, themeasurement platform 230 may be located on the anterior side 240 of thewearer's wrist where the subsurface vasculature may be readilyobservable. However, other configurations are contemplated.

The display 270 may be configured to display a visual indication of thealert or recommendation and/or an indication of the measuredphysiological parameters, for instance, the concentrations of certainblood analytes being measured. Further, the user interface 250 mayinclude one or more buttons 280 for accepting inputs from the wearer.For example, the buttons 280 may be configured to change the text orother information visible on the display 270. As shown in FIG. 2B,measurement platform 230 may also include one or more buttons 290 foraccepting inputs from the wearer. The buttons 290 may be configured toaccept inputs for controlling aspects of the data collection system,such as initiating a measurement period, or inputs indicating thewearer's current health state (i.e., normal, migraine, shortness ofbreath, heart attack, fever, “flu-like” symptoms, food poisoning, etc.).

In another example wrist-mounted device 300, shown in FIGS. 3A-3C, themeasurement platform 310 and user interface 320 are both provided on thesame side of the wearer's wrist, in particular, the anterior side 330 ofthe wrist. On the posterior side 340, a watch face 350 may be disposedon the strap 360. While an analog watch is depicted in FIG. 3B, one ofordinary skill in the art will recognize that any type of clock may beprovided, such as a digital clock.

As can be seen in FIG. 3C, the inner face 370 of the measurementplatform 310 is intended to be worn proximate to the wearer's body. Adata collection system 380 housed on the measurement platform 310 mayinclude a detector 382, a signal source 384 and a collection magnet 386.As described above, the signal source 384 and the collection magnet 386may not be provided in all embodiments of the wearable device.

In a further example shown in FIGS. 4A and 4B, a wrist mounted device400 includes a measurement platform 410, which includes a datacollection system 420, disposed on a strap 430. Inner face 440 ofmeasurement platform may be positioned proximate to a body surface sothat data collection system 420 may interrogate the subsurfacevasculature of the wearer's wrist. A user interface 450 with a display460 may be positioned facing outward from the measurement platform 410.As described above in connection with other embodiments, user interface450 may be configured to display data collected from the data collectionsystem 420, including the concentration of one or more measuredanalytes, and one or more alerts generated by a remote server or otherremote computing device, or a processor located on the measurementplatform. The user interface 420 may also be configured to display thetime of day, date, or other information that may be relevant to thewearer.

As shown in FIG. 5, in a further embodiment, wrist-mounted device 500may be provided on a cuff 510. Similar to the previously discussedembodiments, device 500 includes a measurement platform 520 and a userinterface 530, which may include a display 540 and one or more buttons550. The display 540 may further be a touch-screen display configured toaccept one or more input by the wearer. For example, as shown in FIG. 6,display 610 may be a touch-screen configured to display one or morevirtual buttons 620 for accepting one or more inputs for controllingcertain functions or aspects of the device 600, or inputs of informationby the user, such as current health state.

FIG. 7 is a simplified schematic of a system including one or morewearable devices 700. The one or more wearable devices 700 may beconfigured to transmit data via a communication interface 710 over oneor more communication networks 720 to a remote server 730. In oneembodiment, the communication interface 710 includes a wirelesstransceiver for sending and receiving communications to and from theserver 730. In further embodiments, the communication interface 710 mayinclude any means for the transfer of data, including both wired andwireless communications. For example, the communication interface mayinclude a universal serial bus (USB) interface or a secure digital (SD)card interface. Communication networks 720 may be any one of may be oneof: a plain old telephone service (POTS) network, a cellular network, afiber network and a data network. The server 730 may include any type ofremote computing device or remote cloud computing network. Further,communication network 720 may include one or more intermediaries,including, for example wherein the wearable device 700 transmits data toa mobile phone or other personal computing device, which in turntransmits the data to the server 730.

In addition to receiving communications from the wearable device 700,such as collected physiological parameter data and data regarding healthstate as input by the user, the server may also be configured to gatherand/or receive either from the wearable device 700 or from some othersource, information regarding a wearer's overall medical history,environmental factors and geographical data. For example, a user accountmay be established on the server for every wearer that contains thewearer's medical history. Moreover, in some examples, the server 730 maybe configured to regularly receive information from sources ofenvironmental data, such as viral illness or food poisoning outbreakdata from the Centers for Disease Control (CDC) and weather, pollutionand allergen data from the National Weather Service. Further, the servermay be configured to receive data regarding a wearer's health state froma hospital or physician. Such information may be used in the server'sdecision-making process, such as recognizing correlations and ingenerating clinical protocols.

Additionally, the server may be configured to gather and/or receive thedate, time of day and geographical location of each wearer of the deviceduring each measurement period. Such information may be used to detectand monitor spatial and temporal spreading of diseases. As such, thewearable device may be configured to determine and/or provide anindication of its own location. For example, a wearable device mayinclude a GPS system so that it can include GPS location information(e.g., GPS coordinates) in a communication to the server. As anotherexample, a wearable device may use a technique that involvestriangulation (e.g., between base stations in a cellular network) todetermine its location. Other location-determination techniques are alsopossible.

The server may also be configured to make determinations regarding theefficacy of a drug or other treatment based on information regarding thedrugs or other treatments received by a wearer of the device and, atleast in part, the physiological parameter data and the indicated healthstate of the user. From this information, the server may be configuredto derive an indication of the effectiveness of the drug or treatment.For example, if a drug is intended to treat nausea and the wearer of thedevice does not indicate that he or she is experiencing nausea afterbeginning a course of treatment with the drug, the server may beconfigured to derive an indication that the drug is effective for thatwearer. In another example, a wearable device may be configured tomeasure blood glucose. If a wearer is prescribed a drug intended totreat diabetes, but the server receives data from the wearable deviceindicating that the wearer's blood glucose has been increasing over acertain number of measurement periods, the server may be configured toderive an indication that the drug is not effective for its intendedpurpose for this wearer.

Further, some embodiments of the system may include privacy controlswhich may be automatically implemented or controlled by the wearer ofthe device. For example, where a wearer's collected physiologicalparameter data and health state data are uploaded to a cloud computingnetwork for trend analysis by a clinician, the data may be treated inone or more ways before it is stored or used, so that personallyidentifiable information is removed. For example, a user's identity maybe treated so that no personally identifiable information can bedetermined for the user, or a user's geographic location may begeneralized where location information is obtained (such as to a city,ZIP code, or state level), so that a particular location of a usercannot be determined.

Additionally or alternatively, wearers of a device may be provided withan opportunity to control whether or how the device collects informationabout the wearer (e.g., information about a user's medical history,social actions or activities, profession, a user's preferences, or auser's current location), or to control how such information may beused. Thus, the wearer may have control over how information iscollected about him or her and used by a clinician or physician or otheruser of the data. For example, a wearer may elect that data, such ashealth state and physiological parameters, collected from his or herdevice may only be used for generating an individual baseline andrecommendations in response to collection and comparison of his or herown data and may not be used in generating a population baseline or foruse in population correlation studies.

III. Example Electronics Platform for a Wearable Device

FIG. 8 is a simplified block diagram illustrating the components of awearable device 800, according to an example embodiment. Wearable device800 may take the form of or be similar to one of the wrist-mounteddevices 200, 300, 400, 500, 600, shown in FIGS. 2A-B, 3A-3C, 4A-4C, 5and 6. However, wearable device 800 may also take other forms, such asan ankle, waist, or chest-mounted device.

In particular, FIG. 7 shows an example of a wearable device 800 having adata collection system 810, a user interface 820, communication platform830 for transmitting data to a server, and processor(s) 840. Thecomponents of the wearable device 800 may be disposed on a mount 850 formounting the device to an external body surface where a portion ofsubsurface vasculature is readily observable.

Processor 840 may be a general-purpose processor or a special purposeprocessor (e.g., digital signal processors, application specificintegrated circuits, etc.). The one or more processors 840 can beconfigured to execute computer-readable program instructions 870 thatare stored in the computer readable medium 860 and are executable toprovide the functionality of a wearable device 800 described herein.

The computer readable medium 860 may include or take the form of one ormore non-transitory, computer-readable storage media that can be read oraccessed by at least one processor 840. The one or morecomputer-readable storage media can include volatile and/or non-volatilestorage components, such as optical, magnetic, organic or other memoryor disc storage, which can be integrated in whole or in part with atleast one of the one or more processors 840. In some embodiments, thecomputer readable medium 860 can be implemented using a single physicaldevice (e.g., one optical, magnetic, organic or other memory or discstorage unit), while in other embodiments, the computer readable medium860 can be implemented using two or more physical devices.

Data collection system 810 includes a detector 812 and, in someembodiments, a signal source 814. As described above, detector 812 mayinclude any detector capable of detecting at least one physiologicalparameter, which could include any parameters that may relate to thehealth of the person wearing the wearable device. For example, thedetector 812 could be configured to measure blood pressure, pulse rate,skin temperature, etc. At least one of the detectors 812 is configuredto non-invasively measure one or more analytes in blood circulating insubsurface vasculature proximate to the wearable device. In someexamples, detector 812 may include one or more of an optical (e.g.,CMOS, CCD, photodiode), acoustic (e.g., piezoelectric, piezoceramic),electrochemical (voltage, impedance), thermal, mechanical (e.g.,pressure, strain), magnetic, or electromagnetic (e.g., magneticresonance) sensor.

In some examples, the data collection system 810 further includes asignal source 814 for transmitting an interrogating signal that canpenetrate the wearer's skin into the portion of subsurface vasculature.In general, signal source 814 will generate an interrogation signal thatwill produce a responsive signal that can be detected by one or more ofthe detectors 812. The interrogating signal can be any kind of signalthat is benign to the wearer, such as electromagnetic, magnetic, optic,acoustic, thermal, mechanical, and results in a response signal that canbe used to measure a physiological parameter or, more particularly, thatcan detect the binding of the clinically-relevant analyte to thefunctionalized particles. In one example, the interrogating signal is anelectromagnetic pulse (e.g., a radio frequency (RF) pulse) and theresponse signal is a magnetic resonance signal, such as nuclear magneticresonance (NMR). In another example, the interrogating signal is atime-varying magnetic field, and the response signal is anexternally-detectable physical motion due to the time-varying magneticfield. The time-varying magnetic field modulates the particles byphysical motion in a manner different from the background, making themeasier to detect. In a further example, the interrogating signal is anelectromagnetic radiation signal. In particular, the interrogatingsignal may be electromagnetic radiation having a wavelength betweenabout 400 nanometers and about 1600 nanometers. The interrogating signalmay, more particularly, comprise electromagnetic radiation having awavelength between about 500 nanometers and about 1000 nanometers. Inexamples where the functionalized particles include a fluorophore, theinterrogating signal may therefore be an electromagnetic radiationsignal with a wavelength that can excite the fluorophore and penetratethe skin or other tissue and subsurface vasculature (e.g., a wavelengthin the range of about 500 to about 1000 nanometers), and the responsesignal is fluorescence radiation from the fluorophore that can penetratethe subsurface vasculature and tissue to reach the detector.

The program instructions 870 stored on the computer readable medium 860may include instructions to perform or facilitate some or all of thedevice functionality described herein. For instance, in the illustratedembodiment, program instructions 870 include a controller module 872,calculation and decision module 874 and an alert module 876.

The controller module 872 can include instructions for operating thedata collection system 810, for example, the detector 812 and signalsource 814. For example, the controller 872 may activate signal source814 and/or detector 812 during each of the pre-set measurement periods.In particular, the controller module 872 can include instructions forcontrolling the signal source 814 to transmit an interrogating signal atpreset measurement times and controlling the detector 812 to receivedata representative of response signals transmitted from the portion ofsubsurface vasculature in response to the interrogating signalstransmitted at the preset measurement times.

The controller module 872 can also include instructions for operating auser interface 820. For example, controller module 872 may includeinstructions for displaying data collected by the data collection system810 and analyzed by the calculation and decision module 874, or fordisplaying one or more alerts generated by the alert module 875.Further, controller module 872 may include instructions to executecertain functions based on inputs accepted by the user interface 820,such as inputs accepted by one or more buttons disposed on the userinterface.

Communication interface 730 may also be operated by instructions withinthe controller module 872, such as instructions for sending and/orreceiving information via a wireless antenna, which may be disposed onor in the wearable device 800. The communication interface 830 canoptionally include one or more oscillators, mixers, frequency injectors,etc. to modulate and/or demodulate information on a carrier frequency tobe transmitted and/or received by the antenna. In some examples, thewearable device 800 is configured to indicate an output from theprocessor by modulating an impedance of the antenna in a manner that isperceivable by a remote server or other remote computing device.

Calculation and decision module 872 may include instructions forreceiving data from the data collection system 810 in the form of aresponsive signal, analyzing the data to determine if the target analyteis present or absent, quantify the measured physiological parameter(s),such as concentration of a target analyte, and analyzing the data todetermine if a medical condition is indicated. In particular, thecalculation and decision module 872 may include instructions fordetermining, for each preset measurement time, a concentration of aclinically-relevant analyte based on the response signal detected by thedetector at that measurement time and determining, for each presetmeasurement time, whether a medical condition is indicated based on atleast the corresponding concentration of the clinically-relevantanalyte. The preset measurement times may be set to any period and, inone example, are about one hour apart.

The program instructions of the calculation and decision module 872 may,in some examples, be stored in a computer-readable medium and executedby a processor located external to the wearable device. For example, thewearable device could be configured to collect certain data regardingphysiological parameters from the wearer and then transmit the data to aremote server, which may include a mobile device, a personal computer,the cloud, or any other remote system, for further processing.

The computer readable medium 860 may further contain other data orinformation, such as medical and health history of the wearer of thedevice, that may be necessary in determining whether a medical conditionis indicated. Further, the computer readable medium 860 may contain datacorresponding to certain analyte baselines, above or below which amedical condition is indicated. The baselines may be pre-stored on thecomputer readable medium 860, may be transmitted from a remote source,such as a remote server, or may be generated by the calculation anddecision module 874 itself. The calculation and decision module 874 mayinclude instructions for generating individual baselines for the wearerof the device based on data collected over a certain number ofmeasurement periods. For example, the calculation and decision module874 may generate a baseline concentration of a target blood analyte foreach of a plurality of measurement periods by averaging the analyteconcentration at each of the measurement periods measured over thecourse of a few days, and store those baseline concentrations in thecomputer readable medium 860 for later comparison. Baselines may also begenerated by a remote server and transmitted to the wearable device 800via communication interface 830. The calculation and decision module 874may also, upon determining that a medical condition is indicated,generate one or more recommendations for the wearer of the device based,at least in part, on consultation of a clinical protocol. Suchrecommendations may alternatively be generated by the remote server andtransmitted to the wearable device.

In some examples, the collected physiological parameter data, baselineprofiles, health state information input by device wearers and generatedrecommendations and clinical protocols may additionally be input to acloud network and be made available for download by a wearer'sphysician. Trend and other analyses may also be performed on thecollected data, such as physiological parameter data and health stateinformation, in the cloud computing network and be made available fordownload by physicians or clinicians.

Further, physiological parameter and health state data from individualsor populations of device wearers may be used by physicians or cliniciansin monitoring efficacy of a drug or other treatment. For example,high-density, real-time data may be collected from a population ofdevice wearers who are participating in a clinical study to assess thesafety and efficacy of a developmental drug or therapy. Such data mayalso be used on an individual level to assess a particular wearer'sresponse to a drug or therapy. Based on this data, a physician orclinician may be able to tailor a drug treatment to suit an individual'sneeds.

In response to a determination by the calculation and decision module874 that a medical condition is indicated, the alert module 876 maygenerate an alert via the user interface 820. The alert may include avisual component, such as textual or graphical information displayed ona display, an auditory component (e.g., an alarm sound), and/or tactilecomponent (e.g., a vibration). The textual information may include oneor more recommendations, such as a recommendation that the wearer of thedevice contact a medical professional, seek immediate medical attention,or administer a medication.

FIG. 9 is a simplified block diagram illustrating the components of awearable device 900, according to an example embodiment. Wearable device900 is the same as wearable device 800 in all respects, except that thedata collection system 910 of wearable device 900 further includes acollection magnet 916. In this example, the collection magnet 916 may beused to locally collect functionalized magnetic particles present in anarea of subsurface vasculature proximate to the collection magnet 916.As described above, collection magnet 916 is configured to direct amagnetic field into a portion of subsurface vasculature sufficient tocause functionalized magnetic particles to collect in a lumen of theportion of subsurface vasculature.

Wearable device 900 includes a data collection system 910, whichincludes a detector 912, a signal source 914 (if provided) and acollection magnet 916, a user interface 920, a communication interface930, a processor 940 and a computer readable medium 960 on which programinstructions 970 are stored. All of the components of wearable device900 may be provided on a mount 950. In this example, the programinstructions 970 may include a controller module 962, a calculation anddecision module 964 and an alert module 966 which, similar to theexample set forth in FIG. 8, include instructions to perform orfacilitate some or all of the device functionality described herein.Controller module 962 further includes instructions for operatingcollection magnet 916. For example, controller module 962 may includeinstructions for activating collection magnet during a measurementperiod, for a certain amount of time.

III. Illustrative Functionalized Particles

In some examples, the wearable devices described above obtain at leastsome of the health-related information by detecting the binding of aclinically-relevant analyte to functionalized particles, for example,microparticles or nanoparticles. The particles can be functionalized bycovalently attaching a bioreceptor designed to selectively bind orotherwise recognize a particular clinically-relevant analyte. Forexample, particles may be functionalized with a variety of bioreceptors,including antibodies, nucleic acids (DNA, siRNA), low molecular weightligands (folic acid, thiamine, dimercaptosuccinic acid), peptides (RGD,LHRD, antigenic peptides, internalization peptides), proteins (BSA,transferrin, antibodies, lectins, cytokines, fibrinogen, thrombin),polysaccharides (hyaluronic acid, chitosan, dextran, oligosaccharides,heparin), polyunsaturated fatty acids (palmitic acid, phospholipids),plasmids. The functionalized particles can be introduced into theperson's blood stream by injection, ingestion, inhalation,transdermally, or in some other manner.

The clinically-relevant analyte could be any analyte that, when presentin or absent from the blood, or present at a particular concentration orrange of concentrations, may be indicative of a medical condition orindicative that a medical condition may be imminent. For example, theclinically-relevant analyte could be an enzyme, hormone, protein, orother molecule. In one relevant example, certain protein biomarkers areknown to be predictive of an impending arterial plaque rupture. Suchprotein biomarkers are known to be present in the blood only directlyleading up to and at the onset of an arterial plaque rupture. Plaquesthat rupture cause the formation of blood clots that can block bloodflow or break off and travel to another part of the body. In either ofthese cases, if a clot blocks a blood vessel that feeds the heart, itcauses a heart attack. If it blocks a blood vessel that feeds the brain,it causes a stroke. If blood supply to the arms or legs is reduced orblocked, it can cause difficulty walking and eventually gangrene. Thepresence of these protein biomarkers in the vasculature may be detected,and the medical condition (i.e., stroke, heart attack) prevented, byproviding particles functionalized with a bioreceptor that willselectively bind to this target analyte.

The particles may be made of biodegradable or non-biodegradablematerials. For example, the particles may be made of polystyrene.Non-biodegradable particles may be provided with a removal means toprevent harmful buildup in the body. Generally, the particles may bedesigned to have a long half-life so that they remain in the vasculatureor body fluids over several measurement periods. Depending on thelifetime of the particles, however, the user of the wearable device mayperiodically introduce new batches of functionalized particles into thevasculature or body fluids.

Bioreceptors can be used in diagnostic procedures, or even in therapy todestroy a specific target, such as antitumor therapy or targetedchemotherapy. The particles may be designed to remove from the body ordestroy the target analyte once bound to the bioreceptor. Additionalfunctional groups may be added to the particles to signal that theparticles can be removed from the body through the kidneys, for example,once bound to the target analyte.

Further, the particles may be designed to either releasably orirreversibly bind to the target analyte. For example, if it is desiredfor the particles to participate in destruction or removal of the targetanalyte from the body, as described above, the particles may be designedto irreversibly bind to the target analyte. In other examples, theparticles may be designed to release the target analyte aftermeasurement has been made, either automatically or in response to anexternal or internal stimulus.

Those of skill in the art will understand the term “particle” in itsbroadest sense and that it may take the form of any fabricated material,a molecule, cryptophan, a virus, a phage, etc. Further, a particle maybe of any shape, for example, spheres, rods, non-symmetrical shapes,etc. The particles can have a diameter that is less than about 20micrometers. In some embodiments, the particles have a diameter on theorder of about 10 nm to 1 μm. In further embodiments, small particles onthe order of 10-100 nm in diameter may be assembled to form a larger“clusters” or “assemblies on the order of 1-10 micrometers. In thisarrangement, the assemblies would provide the signal strength of alarger particle, but would be deformable, thereby preventing blockagesin smaller vessels and capillaries.

Binding of the functionalized particles to a target analyte may bedetected with or without a stimulating signal input. The term “binding”is understood in its broadest sense to include any detectableinteraction between the receptor and the target analyte. For example,some particles may be functionalized with compounds or molecules, suchas fluorophores or autofluorescent, luminescent or chemo-luminescentmarkers, which generate a responsive signal when the particles bind tothe target analyte without the input of a stimulus. In other examples,the functionalized particles may produce a different responsive signalin their bound versus unbound state in response to an external stimulus,such as an electromagnetic, acoustic, optical, or mechanical energy.

Further, the particles may be formed from a paramagnetic orferromagnetic material or be functionalized with a magnetic moiety. Themagnetic properties of the particles can be exploited in magneticresonance detection schemes to enhance detection sensitivity. In anotherexample, an external magnet may be used to locally collect the particlesin an area of subsurface vasculature during a measurement period. Suchcollection may not only increase the differential velocity betweenparticles and analytes, hence surveying a much larger volume per unittime, but may also enhance the signal for subsequent detection.

IV. Illustrative Methods for Operation of a Wearable Device

FIG. 10 is a flowchart of a method 1000 for operating a wearable deviceto take non-invasive, in vivo, real-time measurements of physiologicalparameters. A wearable device is first mounted to a body surface of ahuman subject, wherein the body surface is proximate to a portion ofsubsurface vasculature (1010). In some examples, the wearable device,via a signal source, transmits an interrogating signal into the portionof subsurface vasculature (1020). The wearable device, via a detector,then detects a response signal transmitted from the portion ofsubsurface vasculature, wherein the response signal is related tobinding of a clinically-relevant analyte to functionalized particlespresent in a lumen of the subsurface vasculature (1030). In someexamples, the response signal is generated in response to aninterrogating signal. The functionalized particles are configured tobind to the clinically-relevant analyte and may comprise a receptor,such as an antibody. The term “bind” is understood in its broadest senseto also include any detectable interaction between the clinicallyrelevant analyte and the functionalized particles. The wearable devicethen determines the presence, absence and/or a concentration of theclinically-relevant analyte based on the response signal (1040) andwhether a medical condition is indicated based on at least the presence,absence and/or concentration of the clinically-relevant analyte (1040).Further, in examples where the functionalized particles are magnetic,the wearable device may further direct a magnetic field into the portionof subsurface vasculature, the magnetic field being sufficient to causethe functionalized magnetic particles to collect in a lumen of theportion of subsurface vasculature.

FIGS. 11A-11B, 12A-12B, and 13A-13B are partial cross-sectional sideviews of a human wrist illustrating the operation of various examples ofa wrist-mounted device. In the example shown in FIGS. 11A and 11B, thewrist-mounted device 1100 includes a measurement platform 1110 mountedon a strap or wrist-band 1120 and oriented on the anterior side 1190 ofthe wearer's wrist. Measurement platform 1110 is positioned over aportion of the wrist where subsurface vasculature 1130 is easilyobservable. Functionalized particles 1140 have been introduced into alumen of the subsurface vasculature by one of the means discussed above.In this example, measurement platform 1110 includes a data collectionsystem having both a detector 1150 and a signal source 1160. FIG. 11Aillustrates the state of the subsurface vasculature when measurementdevice 1100 is inactive. The state of the subsurface vasculature duringa measurement period is illustrated in FIG. 11B. At this time, signalsource 1160 is transmitting an interrogating signal 1162 into theportion of subsurface vasculature and detector 1150 is receiving aresponse signal 1152 generated in response to the interrogating signal1162. The response signal 1152 is related to the binding of a clinicallyrelevant analyte present in the subsurface vasculature to thefunctionalized particles 1140. As described above, in some embodiments,an interrogating signal may not be necessary to generate a responsesignal related to the binding of an analyte to the functionalizedparticles.

Similar to the system depicted in FIGS. 11A and 11B, FIGS. 12A and 12Billustrate a wrist-mounted device 1200 including a measurement platform1210 mounted on a strap or wristband 1220 and oriented on the anteriorside 1290 of the wearer's wrist. In this example, measurement platform1210 includes a data collection system having a detector 1250, a signalsource 1260 and a collection magnet 1270. FIG. 12A illustrates the stateof the subsurface vasculature when measurement device 1200 is inactive.The state of the subsurface vasculature when measurement device 1200 isactive during a measurement period is illustrated in FIG. 12B. At thistime, collection magnet 1270 generates a magnetic field 1272 sufficientto cause functionalized magnetic particles 1240 present in a lumen ofthe subsurface vasculature 1230 to collection in a region proximal tothe magnet 1270. Signal source 1260 transmits an interrogating signal1262 into the portion of subsurface vasculature and detector 1250 isreceiving a response signal 1252 generated in response to theinterrogating signal 1262. The response signal 1252 is related to thebinding of a clinically relevant analyte present in the subsurfacevasculature to the functionalized magnetic particles 1240. As describedabove, in some embodiments, an interrogating signal may not be necessaryto generate a response signal related to the binding of an analyte tothe functionalized magnetic particles.

FIGS. 13A and 13B illustrate a further embodiment of a wrist-mounteddevice 1300 having a measurement platform 1310 disposed on a strap 1320,wherein the detector 1350 and signal source 1360 are positioned on theposterior side 1390 of the wearer's wrist and the collection magnet 1370is disposed on the anterior side 1380 of the wearer's wrist. Similar tothe embodiments discussed above, FIG. 13A illustrates the state of thesubsurface vasculature when measurement device 1300 is inactive. Thestate of the subsurface vasculature when measurement device 1300 isactive during a measurement period is illustrated in FIG. 13B. At thistime, collection magnet 1370 generates a magnetic field 1232 sufficientto cause functionalized magnetic particles 1340 present in a lumen ofthe subsurface vasculature 1330 to collection in a region proximal tothe magnet 1370. Signal source 1360 transmits an interrogating signal1362 into the portion of subsurface vasculature and detector 1350 isreceiving a response signal 1352 generated in response to theinterrogating signal 1262. The response signal 1352 is related to thebinding of a clinically relevant analyte present in the subsurfacevasculature to the functionalized magnetic particles 1340. As describedabove, in some embodiments, an interrogating signal may not be necessaryto generate a response signal related to the binding of an analyte tothe functionalized magnetic particles.

Both FIGS. 12B and 13B illustrate the path of the interrogating signal(1262, 1362) transmitted by the signal source (1260, 1360) and theresponsive signal (1252, 1352) detected by the detector (1250, 1350)essentially overlapping over a portion of subsurface vasculature. Insome examples, the signal source (1260, 1360) and the detector (1250,1350) may be angled towards each other so that they are interrogatingand detecting from essentially the same area of subsurface vasculature.However, in some instances, such as in the example shown in FIG. 11B,the paths of the interrogating signal (1262, 1362) transmitted by thesignal source (1260, 1360) and the responsive signal (1252, 1352)detected by the detector (1250, 1350) may not overlap.

While various aspects and embodiments have been disclosed herein, otheraspects and embodiments will be apparent to those skilled in the art.The various aspects and embodiments disclosed herein are for purposes ofillustration and are not intended to be limiting, with the true scopebeing indicated by the following claims.

V. Conclusion

Where example embodiments involve information related to a person or adevice of a person, some embodiments may include privacy controls. Suchprivacy controls may include, at least, anonymization of deviceidentifiers, transparency and user controls, including functionalitythat would enable users to modify or delete information relating to theuser's use of a product.

Further, in situations in where embodiments discussed herein collectpersonal information about users, or may make use of personalinformation, the users may be provided with an opportunity to controlwhether programs or features collect user information (e.g., informationabout a user's medical history, social network, social actions oractivities, profession, a user's preferences, or a user's currentlocation), or to control whether and/or how to receive content from thecontent server that may be more relevant to the user. In addition,certain data may be treated in one or more ways before it is stored orused, so that personally identifiable information is removed. Forexample, a user's identity may be treated so that no personallyidentifiable information can be determined for the user, or a user'sgeographic location may be generalized where location information isobtained (such as to a city, ZIP code, or state level), so that aparticular location of a user cannot be determined. Thus, the user mayhave control over how information is collected about the user and usedby a content server.

What is claimed is:
 1. A wearable device, comprising: a mount formounting the wearable device to an external surface of a body proximateto a portion of subsurface vasculature; a magnet; a detector; acommunication interface; a processor; a non-transitory computer-readablemedium; and program instructions stored in the non-transitorycomputer-readable medium, wherein the program instructions areexecutable by the processor to cause the wearable device to performfunctions comprising: operating the magnet to direct a magnetic fieldinto the portion of subsurface vasculature, wherein the magnetic fieldcauses functionalized magnetic nanoparticles that have been introducedinto the body to collect in a lumen of the portion of subsurfacevasculature, wherein the functionalized magnetic nanoparticles eachcomprise an antibody and a marker, wherein the marker is a fluorophore,an autofluorescent marker, a luminescent marker, or a chemo-luminescentmarker, and wherein the marker produces fluorescence radiationindicative of an analyte; operating the detector to detect thefluorescence radiation produced by the marker in the functionalizedmagnetic nanoparticles collected in the lumen of the subsurfacevasculature by the magnetic field; using the fluorescence radiationdetected by the detector to detect a presence of the analyte;determining whether the presence of the analyte indicates a medicalcondition; and in response to a determination that the medical conditionis indicated, transmitting data representative of the medical conditionvia the communication interface.
 2. The wearable device of claim 1,wherein the external surface of the body comprises a wrist.
 3. Thewearable device of claim 2, wherein the mount comprises a wristband orcuff.
 4. The wearable device of claim 1, wherein the functions furthercomprise: using the fluorescence radiation detected by the detector todetermine a concentration of the analyte; and determining whether theconcentration of the analyte indicates a medical condition.
 5. Thewearable device of claim 1, further comprising: a signal source, whereinthe functions further comprise operating the signal source to transmitan interrogating signal into the portion of subsurface vasculature,wherein the fluorescence radiation is produced in response to theinterrogating signal.
 6. The wearable device of claim 5, wherein theinterrogating signal comprises electromagnetic radiation having awavelength between about 400 nanometers and about 1600 nanometers. 7.The wearable device of claim 6, wherein the interrogating signalcomprises electromagnetic radiation having a wavelength between about500 nanometers and about 1000 nanometers.
 8. The wearable device ofclaim 6, wherein the marker in the functionalized magnetic nanoparticlesis a fluorophore.
 9. The wearable device of claim 1, wherein the markerin the functionalized magnetic nanoparticles is a chemo-luminescentmarker.
 10. The wearable device of claim 1, further comprising: a userinterface, wherein the functions further comprise: reporting thepresence of the analyte via the user interface.
 11. The wearable deviceof claim 10, wherein the functions further comprise: in response to adetermination that the medical condition is indicated, generating analert via the user interface.
 12. The wearable device of claim 5,wherein the functions further comprise: controlling the signal source totransmit interrogating signals at preset measurement times; receiving,from the detector, data representative of fluorescence radiationtransmitted from the portion of subsurface vasculature in response tothe interrogating signals transmitted at the preset measurement times;for each preset measurement time, using the fluorescence radiationdetected by the detector at that measurement time to detect the presenceof the analyte; and determining, for each preset measurement time,whether the presence of the analyte indicates the medical condition. 13.The wearable device of claim 12, wherein the functions further comprise:for each preset measurement time, using the fluorescence radiationdetected by the detector at that measurement time to determine acorresponding concentration of the analyte; and determining, for eachpreset measurement time, whether the corresponding concentration of theanalyte indicates the medical condition.
 14. The wearable device ofclaim 1, wherein the magnet is an electromagnet.